2,024 research outputs found

    Modulation of the slow/common gating of CLC channels by intracellular cadmium.

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    Members of the CLC family of Cl(-) channels and transporters are homodimeric integral membrane proteins. Two gating mechanisms control the opening and closing of Cl(-) channels in this family: fast gating, which regulates opening and closing of the individual pores in each subunit, and slow (or common) gating, which simultaneously controls gating of both subunits. Here, we found that intracellularly applied Cd(2+) reduces the current of CLC-0 because of its inhibition on the slow gating. We identified CLC-0 residues C229 and H231, located at the intracellular end of the transmembrane domain near the dimer interface, as the Cd(2+)-coordinating residues. The inhibition of the current of CLC-0 by Cd(2+) was greatly enhanced by mutation of I225W and V490W at the dimer interface. Biochemical experiments revealed that formation of a disulfide bond within this Cd(2+)-binding site is also affected by mutation of I225W and V490W, indicating that these two mutations alter the structure of the Cd(2+)-binding site. Kinetic studies showed that Cd(2+) inhibition appears to be state dependent, suggesting that structural rearrangements may occur in the CLC dimer interface during Cd(2+) modulation. Mutations of I290 and I556 of CLC-1, which correspond to I225 and V490 of CLC-0, respectively, have been shown previously to cause malfunction of CLC-1 Cl(-) channel by altering the common gating. Our experimental results suggest that mutations of the corresponding residues in CLC-0 change the subunit interaction and alter the slow gating of CLC-0. The effect of these mutations on modulations of slow gating of CLC channels by intracellular Cd(2+) likely depends on their alteration of subunit interactions

    Blast Load Input Estimation of the Medium Girder Bridgeusing Inverse Method

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    Innovative adaptive weighted input estimation inverse methodology for estimating theunknown time-varying blast loads on the truss structure system is presented. This method isbased on the Kalman filter and the recursive least square estimator (RLSE). The filter models thesystem dynamics in a linear set of state equations. The state equations of the truss structureare constructed using the finite element method. The input blast loads of the truss structuresystem are inverse estimated from the system responses measured at two distinct nodes. Thiswork presents an efficient weighting factor  applied in the RLSE, which is capable of providinga reasonable estimation results. The results obtained from the simulations show that the methodis effective in estimating input blast loads, so has great stability and precision.Defence Science Journal, 2008, 58(1), pp.46-56, DOI:http://dx.doi.org/10.14429/dsj.58.162

    Determination of Moving Tank and Missile ImpactForces on a Bridge Structure

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    A method to determine the moving tank and missile impact forces on a bridge is developed. The presentmethod is an online adaptive recursive inverse algorithm, which is composed of the Kalman filter  and therecursive least square estimator (RLSE), to estimate the force inputs on the bridge structure. The state equationsof the bridge structure were constructed by using the model superposition and orthogonal technique. Byadopting this inverse method, the moving tank and missile impact force inputs acting on the bridge structuresystem can be estimated from the measured dynamic responses. Besides, this work presents an efficientweighting factor applied in the RLSE, which is capable of providing a reasonable estimation results. The resultsobtained from the simulations show that the method is effective in determining the moving tank and missileimpact forces, so that the acceptable results can be obtained.Defence Science Journal, 2008, 58(6), pp.752-761, DOI:http://dx.doi.org/10.14429/dsj.58.170

    Minimizing Design Costs of an FIR Filter Using a Novel Coefficient Optimization Algorithm

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    This work presents a novel coefficient optimization algorithm to reduce the area and improve the performance of finite impulse response (FIR) filter designs. Two basic architectures are commonly used in filters—direct and transposed. The coefficients of a filter can be encoded in the fewest possible nonzero bits using canonic signed digit (CSD) expressions. The proposed optimization algorithm can share common subexpressions (CS) and reduce the number of replicate operations that involve the CSD coefficients of filters with a transposed architecture. The effectiveness of the algorithm is confirmed by using filters with the collision detection multiple access (CDMA) standard, the 121-tap high-pass band, and 105- and 325-tap low-pass bands as benchmarks. For example, the proposed algorithm used in the optimization of 105-tap filter has a 30.44% smaller combinational logic area and a 16.69% better throughput/area than those of the best design that has been developed to date. Experimental results reveal that the proposed algorithm outperforms earlier designs

    Power Allocation and Time-Domain Artificial Noise Design for Wiretap OFDM with Discrete Inputs

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    Optimal power allocation for orthogonal frequency division multiplexing (OFDM) wiretap channels with Gaussian channel inputs has already been studied in some previous works from an information theoretical viewpoint. However, these results are not sufficient for practical system design. One reason is that discrete channel inputs, such as quadrature amplitude modulation (QAM) signals, instead of Gaussian channel inputs, are deployed in current practical wireless systems to maintain moderate peak transmission power and receiver complexity. In this paper, we investigate the power allocation and artificial noise design for OFDM wiretap channels with discrete channel inputs. We first prove that the secrecy rate function for discrete channel inputs is nonconcave with respect to the transmission power. To resolve the corresponding nonconvex secrecy rate maximization problem, we develop a low-complexity power allocation algorithm, which yields a duality gap diminishing in the order of O(1/\sqrt{N}), where N is the number of subcarriers of OFDM. We then show that independent frequency-domain artificial noise cannot improve the secrecy rate of single-antenna wiretap channels. Towards this end, we propose a novel time-domain artificial noise design which exploits temporal degrees of freedom provided by the cyclic prefix of OFDM systems {to jam the eavesdropper and boost the secrecy rate even with a single antenna at the transmitter}. Numerical results are provided to illustrate the performance of the proposed design schemes.Comment: 12 pages, 7 figures, accepted by IEEE Transactions on Wireless Communications, Jan. 201

    Impact of interleukin-28B polymorphism on HCV-1 infected patients treated with response-guided therapy

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    SummaryBackgroundSingle nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) were associated with sustained virological response (SVR) in hepatitis C virus genotype 1 (HCV-1) infected patients treated with a standard 48-week regimen of peginterferon and ribavirin combination. Whether IL28B SNP genotype would be the influential prognosticator for patients treated with response-guided therapy (RGT) is still not well understood.AimsTo investigate the impact of IL28B rs809917 genotype on HCV-1 infected patients treated with RGT.MethodsA total of 128 consecutive treatment-naïve HCV-1 infected patients between July 2006 and July 2011 were analyzed. For rapid virological response (RVR) patients, we allowed an abbreviated 24-week regimen regardless of baseline viral loads; otherwise, a 48-week regimen was implemented (for patients with early virological response). The IL28B rs8099917 SNP genotypes were determined accordingly.ResultsA total of 117 patients (91.4%) were of rs8099917 TT genotype and 11 (8.6%) were of GT/GG genotype. Eighty-two of the 128 (64.1%) patients achieved SVR, occurring in 54 of 67 RVR patients (80.6%) and 28 of 61 non-RVR patients (45.9%, p < 0.001). Compared to the GT/GG genotype, patients with the TT genotype had significantly higher SVR rates (67.5% vs. 27.3%; p = 0.008) and low relapse rates (28.2% vs. 70.0%; p = 0.006). The multivariate analysis showed that RVR (odds ratio, 4.51; 95% confidence interval, 1.87–10.90; p = 0.001) and rs8099917 TT genotype (odds ratio, 6.91; 95% confidence interval, 1.53–31.17; p = 0.012) were independent factors associated with SVR.ConclusionFor HCV-1 infected patients who were treated with RGT, the IL28B unfavorable genotype predicted a higher relapse rate; RVR and IL28B favorable genotype were independent factors associated with SVR in patients treated with RGT
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